Regulation of chromosome 21-directed anti-viral gene(s) as a consequence of age

Abstract

WHEN human fibroblast cells are cultured in vitro they undergo about 50 cell population doublings at which time their growth rate begins to slow down and they finally die^1,2. For this reason, several investigators have used the senescence of human fibroblasts in vitro as a model system for experimental ageing research^3–6. One explanation for human fibroblast senescence is that some cell functions are lost before cells reach their maximum division limit. We have described the existence of a complex regulatory gene function controlling the inducibility of chromosome 21-directed anti-viral gene(s) (AVG) in human fibroblasts⁷. Our conclusions were derived from experiments on human fibroblasts monosomic, disomic or trisomic for chromosome 21. We therefore used all three cell types in this study to test the preservation of this complex regulatory gene function in fibroblasts allowed to age in vitro and in fibroblasts derived from human donors of different ages. We found (1) that no differences exist in AVG expression in human fibroblasts allowed to age in vitro and (2) that the AVG in human fibroblasts derived from older human donors (64 yr) is easier to induce than it is in younger donors (0–29 yr).